Gout is a highly prevalent, painful inflammatory arthritis, caused by crystallization of uric acid in joint tissues. Gout flares cause impaired quality of life and physical function, leading to lost work days, disability, high healthcare costs. Patients with gout are also known to be at an increased risk of cardiovascular diseases (CVD), kidney disease, and mortality. Previous studies suggest a potential beneficial effect of urate-lowering therapy on the risk of CVD and renal function. Over the past decade, the American College of Rheumatology and the European League Against Rheumatism recommend a treat-to-target (TTT) approach that lowers serum uric acid (SUA) level below 6 mg/dl to reduce acute gout attacks, based on the upper limit of water solubility of uric acid under normal physiologic circumstances. However, the 2016 American College of Physicians (ACP)? guidelines for gout management recommend use of urate-lowering therapy but support a ?treat-to-avoid symptoms? strategy without monitoring SUA rather than the TTT strategy because of ?inconclusive? evidence in the literature. Such discrepancies in treatment guidelines from various societies urge the need for comparative effectiveness research of the treatment strategies for gout. Rigorous epidemiologic studies utilizing high-quality observational data from electronic health records (EHR) or insurance claims databases can be an important tool for comparative effectiveness research. The primary objective of this 3-year proposal is to provide high-quality, timely evidence on the comparative effectiveness of two different treatment strategies, TTT versus usual care, for management of gout. We will pursue this objective by utilizing the linked Partners? EHR-Medicare database (2007-2016); this linked database includes all patients aged ?65 years enrolled in Medicare Parts A/B/D who had ?1 encounter at one of the Partners Healthcare hospitals. We will have longitudinal, clinically important data on patients? demographics, body mass index, visit notes, laboratory results including SUA and serum creatinine, as well as all Medicare claims for inpatient and outpatient visits, procedures, and prescription drugs. The two specific aims of this 3-year proposal are: 1) to examine the effect of TTT strategy on the risk of gout flares versus usual care and 2) to assess the effect of TTT strategy on the risk of kidney disease and CVD versus usual care. Given the substantial prevalence of gout, the suboptimal management of gout and lack of comparative trial of different treatment strategies, this proposed study will make an immediate, important contribution to the management of gout in clinical practice. This work will not only investigate the effects of different treatment strategies on gout flares but also on common comorbidities in patients with gout such as kidney and CVD. Furthermore, this proposed study will advance understanding of how to improve ascertainment of dynamic outcomes and control for time-varying confounding by utilizing sophisticated and innovative epidemiologic as well as bioinformatics methods in a large EHR database linked with Medicare claims.